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Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.
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Background. The SARS-CoV-2 Omicron variant has been rapidly spreading worldwide. We aimed to characterize Omicron severity by assessing in-hospital deaths and intensive care admissions in a large healthcare system in South Florida during an Omicron predominant surge. Methods. Laboratory-confirmed COVID-19 adult patients hospitalized during January 1 -14, 2022 were retrospectively reviewed. Risks of in-hospital mortality and intensive care admission were estimated using logistic regression models. Analyses were stratified by age >= 65 years and vaccination status, and further adjusted for sex, comorbidities, and history of a previous COVID-19 infection. Results. 500 consecutively hospitalized COVID-19 Omicron patients were included. The median age was 69 (IQR, 53-80) years, and 271 (54.2%) were women. The most common comorbidities were hypertension (65.5%), diabetes (32%), and chronic kidney disease (24%). 260 (52%) patients were fully vaccinated (defined as a patient who received 2-dose vaccines), and 32 (6.4%) were previously infected with COVID-19. 252 (50.4%) patients required supplemental oxygen, 54 (10.8%) required intensive care unit (ICU) admission, and 44 (8.8%) patients required mechanical ventilation. At study closeout of March 7, 2022, case fatality rates among patients aged 18 -29 years, 30 -39 years, 40-49 years, 50-59 years, 60-69 years, 70-79 years, and >= 80 years were 0%, 2.2%, 6.4%, 5.3%, 8.0%, 5.7%, and 15.4% respectively ( p < 0.001), with the median time from hospital admission to death being 13 days (IQR, 6.5-20.5) (Figure 1). Patients aged >= 65 years had 2.6 times higher rates for in-hospital mortality (OR, 2.63;95% CI, 1.29-5.33;p =0.007) than those aged < 65 years, but were comparable for ICU admission (OR, 0.85;95% CI, 0.49-1.52;p =0.586). Past vaccination offered no protection against in-hospital mortality (OR, 1.18;95% CI, 0.64-2.19;p =0.599) or ICU admission (OR, 1.16;95% CI, 0.66-2.06;p =0.6) (Figure 2). In multivariable-adjusted models, patients aged >= 65 years had a higher in-hospital mortality than those aged < 65 years (Figure 2). Conclusion. This case series provides characteristics and outcomes of hospitalized adult patients with COVID-19 Omicron variant. Past COVID-19 vaccination did not impact ICU admission rate nor in-hospital mortality.
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Background. Patients infected with COVID-19 Omicron variant, may be hospitalized for reasons other than COVID-19 pneumonia. We describe the clinical presentations of hospitalized adult patients with COVID-19 Omicron variant in a large healthcare system in South Florida. Methods. Laboratory-confirmed COVID-19 adult patients hospitalized during January 1-14, 2022 were retrospectively reviewed. Clinical presentations were divided into one of three admission groups: COVID-19 pneumonia or respiratory infection (Group 1), severe extrapulmonary manifestations of COVID-19 (Group 2), and completely incidental diagnosis of COVID-19 (Group 3). Risks of in-hospital mortality and intensive care admission were estimated using logistic regression models. Results. Among 500 consecutively hospitalized COVID-19 Omicron patients, the median age was 69 (IQR, 53-80) years, and 271 (54.2%) were women. The most common comorbidities were hypertension (326;65.5%), diabetes (160;32%), and chronic kidney disease (120;24%). 260 (52%) patients were fully vaccinated (defined as a patient who received 2-dose vaccines), and 32 (6.4%) were previously infected with COVID-19. 257(51.4%) patients were classified as Group 1, 82 (16.4%) in Group 2, and 161 (32.2%) in Group 3 (Figure 1). Compared to Group 3, patients in Group 1 and Group 2 had a higher risk for ICU admission, with odds ratios (ORs) of 7.45 (95% CI, 2.62-21.23;p< 0.001) and 4.84 (95% CI, 1.44-16.23;p=0.011), and for in-hospital mortality, with ORs of 27.76 (95% CI, 3.78-204.3;p=0.001) and 12.63 (95% CI, 1.49-106.78;p=0.020), respectively (Figure 2). In multivariable-adjusted models, patients in Group 1 remained at higher risk for ICU admission and in-hospital mortality compared to Group 3, while patients in Group 2 remained at a higher risk for ICU admission, but with no difference in in-hospital mortality compared to Group 3 (Figure 2). Figure 1. Clinical characteristics of consecutively hospitalized patients stratified by clinical presentations at admission. Figure 2. Crude (Upper panel) and multivariable-adjusted (Lower panel) odds ratios for ICU admission and in-hospital mortality from logistic regression models. Group 3 represents patients with a completely incidental diagnosis of COVID-19. The variables included in the final multivariable models were age, gender, history of hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, malignancy, transplantation, HIV, vaccination status, and previous SARS-CoV-2 infection. Conclusion. This case series illustrates the clinical presentations of hospitalized adult patients infected with the COVID-19 Omicron variant. Significant differences in in-hospital mortality and ICU admission exist when comparing patients admitted for a COVID-19 related respiratory infection to those admitted with a completely incidental COVID-19 diagnosis.
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We replicate the test of a theoretical framework put forward and tested by Goldberg et al. (2022) on financial incentives to send peers information about health behaviors. The study we replicate validated the theory in the context of tuberculosis testing in India. We adapt the intervention to preventative COVID-19-related behaviors in Zambia. Similar to the India study, individuals respond favorably to the suggestion to pass messages to peers;however, unlike in India, financial incentives neither generate further passing of messages nor cause changes in health behaviors. We discuss the contextual differences that may explain why key results failed to replicate.
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INTRODUCTION: It is recommended to administer the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy. We evaluated whether the COVID-19 pandemic affected Tdap vaccination during periods when (1) many prenatal visits were via telemedicine and (2) patients might be vaccine wary due to COVID-19 vaccination misinformation. METHODS: This was a retrospective observational study using data queried from the Einstein Healthcare Network electronic medical record. The study included patients who delivered between 2019 and 2021 and their Tdap vaccination status during prenatal care. Chi-square tests compared vaccination rates between patients delivering at different times. RESULTS: Of the pre-pandemic pregnancy control group (n=1,408), 60% received Tdap vaccination. In the second quarter of 2020, when many prenatal visits were done via telemedicine, patients (n=688) were 1.3 times more likely to not receive Tdap vaccination (54%;P=.0033). During the second quarter of 2021, when there was much misinformation regarding COVID-19 vaccination, even with all prenatal visits being in person, patients (n5363) were 1.3 times more likely to not have received the Tdap vaccination (54%;P=.028). True percentages of Tdap vaccination were higher than those reported above due to 16% of patients who received either prenatal care elsewhere or no prenatal care, for whom no vaccination data was available. CONCLUSION: Compared to pre-COVID-19 pandemic, pregnant patients were less likely (OR, 1.3) to have consented to and received the Tdap vaccination during periods when (1) many prenatal visits were via telemedicine and (2) patients might be vaccine wary due to COVID-19 vaccination misinformation.
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G protein-coupled receptor family C group 5 member D (GPRC5D) has limited expression in healthy human tissue but is highly expressed in malignant plasma cells, making it a promising target for immunotherapy approaches for MM. Talquetamab (JNJ-64407564) is a first-in-class bispecific antibody that binds to both GPRC5D and CD3 receptors to redirect T cells to kill MM cells. Updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) are reported (NCT03399799). Eligible patients had RRMM or were intolerant to standard therapies. Patients who were previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range: 5.0-800 μg/kg) weekly (QW) or biweekly (Q2W) with step-up dosing. The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03;cytokine release syndrome (CRS) was graded per Lee et al 2014 criteria. Responses were investigator-assessed per IMWG criteria. As of July 19, 2021, 95 patients had received SC talquetamab. The original RP2D was 405 μg/kg SC talquetamab QW with step-up doses, and a second RP2D of 800 μg/kg SC talquetamab Q2W with step-up doses was also identified. 30 patients received 405 μg/kg QW (median 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up [mF/U]: 7.5 mo [range 0.9-15.2]). 23 patients received 800 μg/kg Q2W (median 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;mF/U: 3.7 mo [range 0.0-12.0]). No treatment discontinuations due to AEs were reported at either RP2Ds. Most common AEs at the 405 μg/kg QW were CRS (73%;1 grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%). Skin-related AEs occurred in 77% of patients and were all grade 1/2 (nail disorders: 30%). Infections occurred in 37% of patients (1 grade 3 COVID-19 pneumonia). Most common AEs at 800 μg/kg Q2W were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%). Skin-related AEs occurred in 65% of patients with grade 3 events in 13% (nail disorders: 17%). Infections occurred in 13% of patients (1 grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated at 405 μg/kg QW, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR]: 57%). In 17 response-evaluable patients treated at 800 μg/ kg Q2W, the ORR was 71% (≥VGPR: 53%). Responses were durable and deepened over time with both RP2Ds (Figure). Median duration of response (DOR) was not reached at either RP2D;6-month DOR rate was 67% (95% CI: 41-84) at 405 μg/kg QW. Serum trough levels of talquetamab were comparable at both RP2Ds. Pharmacodynamic data at both RP2Ds showed peripheral T cell activation and induction of cytokines. SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data suggest that less frequent, higher doses of SC talquetamab do not negatively impact the safety profile. Further evaluation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. (Figure Presented) .
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Background: Early reports suggested that cancer patients have a 1.7-fold increased risk of contracting SARS-CoV-2 and higher rates of severe events and mortality compared with general population. Patients with hematologic malignancies may have worse COVID-19 outcomes, due to an impaired humoral immune response from their underlying malignancy and concurrent anticancer therapy. In this multi-center, retrospective, observational study, we evaluate the associations of COVID-19 outcomes with patient and lymphoma disease characteristics. Methods: EMRs at 10 study centers across the USA identified 519 patients with a diagnosis of lymphoma, CLL, or other lymphoid malignancies, who had a documented positive result of SARS-CoV-2 PCR or nucleocapsid antibody testing. Descriptive statistics were used to summarize the demographic and clinical characteristics. Logistic regression was used to evaluate the associations of individual characteristics with COVID-19 outcomes, adjusted for center (NYU vs. other). The interactions between each of the variables was also included in these models;since the interactions were generally small and non-significant, only the main effect of center was included. Two-sided p-values ≤0.05 were considered significant;there were no adjustments for multiple variables or endpoints. Each analysis was based on complete data for that analysis. Results: Tables 1 and 2 provide demographic and clinical characteristics, respectively, of the 519 patients. The mean age was 61.9 years, with 296 (57%) male and 374 (72%) white patients. NYU had the largest cohort (318 patients), with the remaining centers contributing a range of 3 to 69 patients (median 14). Logistic regression models for the association of each COVID-19 outcome with individual clinical and patient characteristics included adjustments for the center (NYU/other). While center effects were statistically significant, center by covariate interaction effects were not and are not included in the final models. The odds ratio (OR) estimates and p-values for each patient and CLL/lymphoma clinical variable are shown in Tables 3 and 4, respectively. The risks of experiencing a severe event, death, and hospital admission increased with age;for each 10 years of age increase, the ORs were 1.58 for experiencing severe events, 1.78 for death, and 1.65 for hospital admission. The risks of poor outcome were higher in males than in females (OR 1.93 for severe events, 1.85 for death, and 1.47 for hospital admission). Patients with Charlson Comorbidity Index (CCI) >5 had a higher risk of severe events (OR 2.46), mortality (3.30) and hospital admission (2.73) compared to patients with CCI ≤5. Compared to patients with HL, patients with aggressive NHL had a higher risk of severe events (OR 4.05), mortality (4.68) and hospital admission (4.65). Patients with CLL similarly had a higher risk of severe events (OR 4.64), mortality (4.65) and hospital admission (5.93) compared to HL patients. Patients with indolent NHL had a higher risk of hospital admission (OR 3.95) but not a higher risk of mortality compared to HL. Patients in remission at the time of COVID-19 diagnosis had a lower risk of severe events (OR 0.42), mortality (0.36) and hospital admission (0.40) relative to those who were not in remission. Patients who received cytotoxic chemotherapy within 28 days of their COVID-19 diagnosis had a higher risk of severe events (OR 2.54), mortality (2.79), and hospital admission (2.31). Patients who received an anti-CD20 monoclonal antibody within 6 months of COVID-19 diagnosis had a higher risk of severe events (OR 2.60), mortality (2.17) and hospital admission (3.28). Conclusions: In addition to demographic and comorbidity risk factors identified in previous studies, our study shows that patients with aggressive NHL and CLL, or patients who have received recent cytotoxic chemotherapy or anti-CD20 mAB, may be at risk for poor COVID-19 outcome. The difference in risk between NHL and HL patients is likely associated with young age of HL patients but may also be related o differences in underlying innate and adaptive immune defects. Patients at high risk for poor outcome should be a priority for studies of monoclonal antibody prophylaxis. If defects in humoral immunity are at the root of poor outcome, this may be compounded by poor response to vaccination. Multivariate analysis of this data will be completed in advance of the meeting. [Formula presented] Disclosures: Olszewski: Celldex Therapeutics: Research Funding;PrecisionBio: Research Funding;TG Therapeutics: Research Funding;Acrotech Pharma: Research Funding;Genentech, Inc.: Research Funding;Genmab: Research Funding. Barta: Daiichi Sankyo: Honoraria;Seagen: Honoraria;Acrotech: Honoraria;Kyowa Kirin: Honoraria. Hernandez-Ilizaliturri: AbbVie: Other: Advisory Boards;Incyte: Other: Advisory Boards;Celgene: Other: Advisory Boards;BMS: Other: Advisory Boards;Pharmacyclics: Other: Advisory Boards;Amgen: Other: Advisory Boards;Kite: Other: Advisory Boards;Gilead: Other: Advisory Boards;Epyzime: Other: Advisory Boards. Leslie: Janssen: Consultancy, Speakers Bureau;Merck: Consultancy;Abbvie: Consultancy, Honoraria;Epizyme: Consultancy, Honoraria, Speakers Bureau;PCYC/Janssen: Consultancy, Honoraria, Speakers Bureau;Seagen: Consultancy, Honoraria, Speakers Bureau;TG Therapeutics: Consultancy, Honoraria, Speakers Bureau;Celgene/BMS: Consultancy, Honoraria, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy;BeiGene: Consultancy, Honoraria, Speakers Bureau;Karyopharm Therapeutics: Honoraria, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;Pharmacyclics: Consultancy, Honoraria, Speakers Bureau. Diefenbach: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding;Morphosys: Consultancy, Honoraria, Research Funding;Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;Perlmutter Cancer Center at NYU Langone Health: Current Employment;Incyte: Research Funding;AbbVie: Research Funding;Trillium: Research Funding;IGM Biosciences: Research Funding;IMab: Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Gilead: Current equity holder in publicly-traded company;MEI: Consultancy, Research Funding;Celgene: Research Funding;Seattle Genetics: Consultancy, Honoraria, Research Funding.
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Introduction: Despite recent advances in treatment, patients with multiple myeloma (MM) continue to relapse. G protein-coupled receptor family C group 5 member D (GPRC5D) is a promising target for immunotherapy in patients with MM due to its high expression in malignant plasma cells and limited expression in normal human tissue;unlike other antigens targeted by MM therapies, there is no indication that GPRC5D sheds into the periphery. Talquetamab (JNJ-64407564) is a first-in-class bispecific IgG4 antibody that redirects T cells to kill MM cells by binding to both GPRC5D and CD3 receptors. Here we report updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) from a phase 1 trial in relapsed/refractory MM (RRMM;NCT03399799). Methods: Eligible patients with MM had relapsed or refractory disease or were intolerant to standard therapies;patients previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range 5.0-800 µg/kg) weekly or biweekly. Step-up dosing was used as a patient management strategy to minimize the severity of cytokine release syndrome (CRS). The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03 with CRS events graded per Lee et al 2014 criteria. Responses were investigator-assessed per International Myeloma Working Group criteria. Results: As of July 19, 2021, 95 patients have received SC talquetamab. The RP2D was originally identified as a weekly SC dose of 405 µg/kg talquetamab with step-up doses. However, alternative dosing schedules that require less frequent administration continue to be investigated. A biweekly RP2D was also identified as an SC dose of 800 µg/kg talquetamab with step-up doses. 30 patients received the 405 µg/kg weekly dosing schedule (median age: 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up: 7.5 mo [range 0.9-15.2]). 23 patients received the 800 µg/kg biweekly dosing schedule (median age: 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;median follow-up 3.7 mo [range 0.0-12.0]). There were no treatment discontinuations due to AEs at either of the RP2Ds. The most common AEs at the 405 µg/kg weekly dose were CRS (73%;1 patient had grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%);skin-related AEs occurred in 77% (all grade 1/2;nail disorders: 30%) of patients, and infections occurred in 37% of patients (1 patient had grade 3 COVID-19 pneumonia). The most common AEs at the 800 µg/kg biweekly dose were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%);skin-related AEs occurred in 65% of patients (grade 3: 13%;nail disorders: 17%) and infections occurred in 13% of patients (1 patient had grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated with the 405 µg/kg weekly dose, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR] rate: 57%). In 17 response-evaluable patients treated with the 800 µg/kg biweekly dose, the ORR was 71% (≥VGPR rate: 53%). Responses were durable and deepened over time in both cohorts (Figure). Median duration of response (DOR) was not reached at either RP2D;the 6-month DOR rate for patients who received the 405 µg/kg weekly dose was 67% [95% CI: 41-84]. Serum trough levels of talquetamab were comparable at both RP2Ds. Consistent with the mechanism of action for talquetamab, pharmacodynamic data from cohorts treated at both dose levels showed peripheral T-cell activation and induction of cytokines. Conclusions: These findings indicate that SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data from the 800 µg/kg biweekly cohorts indicate that less frequent, higher doses of SC talquetamab do not have a negative impact on the previously described safety profile. Further investigation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. [Formula presented] Disclosures: Krishnan: MAGENTA: Consultancy;BMS: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau;JANSSEN: Consultancy, Research Funding;City of Hope Cancer Center: Current Employment;REGENERON: Consultancy;SANOFI: Consultancy;GSK: Consultancy;Amgen: Speakers Bureau. Minnema: Celgene: Other: Travel expenses;Alnylam: Consultancy;Cilag: Consultancy;BMS: Consultancy;Janssen: Consultancy;Kite/Gilead: Consultancy. Berdeja: Lilly, Novartis: Research Funding;Abbvie, Acetylon, Amgen: Research Funding;Celularity, CRISPR Therapeutics: Research Funding;EMD Sorono, Genentech: Research Funding;Poseida, Sanofi, Teva: Research Funding;Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy;GSK, Ichnos Sciences, Incyte: Research Funding. Oriol: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. van de Donk: Roche: Consultancy;Takeda: Consultancy;Cellectis: Research Funding;Amgen: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;BMS/Celgene: Consultancy, Honoraria;Novartis /bayer/servier: Consultancy. Rodriguez-Otero: Clínica Universidad de Navarra: Current Employment;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria;Regeneron: Honoraria. Askari: Janssen: Research Funding. Mateos: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Honoraria;Bluebird bio: Honoraria;AbbVie: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Costa: BMS: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau;Karyopharm: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria, Speakers Burea . Verona: Janssen: Current Employment. Ma: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Girgis: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Yang: Janssen: Current Employment. Hilder: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Russell: Janssen: Ended employment in the past 24 months. Goldberg: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Chari: Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Research Funding;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Pharmacyclics: Research Funding;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisorycommittees;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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The introduction of post-transplant cyclophosphamide (PTCy) has circumvented the need for T-cell depletion following haploidentical stem cell transplantation (SCT). By expanding the donor pool for patients from certain ethnic minorities, this has addressed to some degree an important health care disparity issue in SCT. However, a recent registry study showed increased incidence GvHD and inferior outcomes in patients receiving haploidentical SCT with PTCy, tacrolimus and mycophenolate mofetil for GvHD prevention as opposed to matched unrelated donor SCT with PTCy-based GvHD prevention. Seeking to improve the results of GvHD prevention in the setting of haploidentical SCT, we examined a combination of PTCy, abatacept and a short course of tacrolimus (CAST). Abatacept is a recombinant soluble fusion protein composed of the extracellular domain of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) fused to the Fc region of IgG1. Abatacept blocks CD28-CD80I86 axis and prevents T-cell co-stimulation. In early studies, abatacept has shown promising results when added to methotrexate and tacrolimus in matched and mismatched donor SCT. We initiated a phase Ib-II clinical trial for patients with hematological malignancies undergoing haploidentical SCT. Patients received G-CSF mobilized peripheral blood grafts from related haploidentical donors. GvHD prevention consisted of PTCy 50mg/kg IV on day +3 and +4 with forced hydration, abatacept 10mg/kg IV on day +5, +14 and +28 and tacrolimus. Tacrolimus was started on day +5 at 0.02mg/kg/day by continuous IV and adjusted thereafter to maintain a trough level of 5-12ng/mL. Tacrolimus taper was planned to begin on day +60 and complete by day +90 in the absence of GvHD. All patients received standard supportive care including levofloxacin until neutrophil engraftment, posaconazole until day +75, acyclovir for 1 year and, if CMV positive by serology, letermovir until day +100. Pneumocystis Jiroveci prophylaxis was started after neutrophil engraftment and continued until 6 months post-transplant. G-CSF was administered routinely until neutrophil engraftment. Since September 2020, 19 patients were enrolled. Three patients are too early in their post-transplant course and were excluded from this analysis. Patients' characteristics are summarized in the table. All but 2 patients received cryopreserved products. Median times to ANC and platelet engraftment were 18.5 days (14-30) and 28.5 (16-61). All 16 patients achieved full whole blood donor chimerism by day +30. There was no secondary graft failure. With a median follow-up was 149.5 days (41-308) with 10 patients having >120 days and 8 >180 days of follow-up, 4 patients developed skin acute GvHD (all grade I). No patient developed grade II-IV acute GvHD. Two patients developed skin chronic GvHD (limited, both moderate). Both cases were diagnosed following COVID-19 vaccination. Fifteen patients completed tacrolimus taper by day +90. Two patients received systemic steroids, one for treatment of cGvHD. The remaining patients required no further immunosuppressive therapy beyond day +90. CMV activation rate was 25%. One patient had EBV reactivation and required preemptive therapy with 2 weekly rituximab doses. There were no cases of adenovirus, HHV-6 virus or BK virus reactivation. Four patients developed renal insufficiency (3 in the setting of acute sepsis and 1 with thrombotic microangiopathy, which resolved after tapering off tacrolimus. One patient with adult T-cell leukemia/lymphoma relapsed and died. All other patients are alive and well. In summary, our preliminary results suggest that CAST with shortened course of tacrolimus is feasible and seems to offer very promising outcomes with low rates of acute GvHD. The study is accruing actively and the results of a larger cohort with longer follow-up will be presented at the meeting. If confirmed, by improving the outcomes of haploidentical SCT, this regimen may further address a health care disparity issue, offering almost every patient in need of allogeneic SCT an alternative donor op ion with equal outcomes. [Formula presented] Disclosures: Al-Homsi: Daichii Sanyko: Consultancy;Celyad: Other: Advisory Board. Abdul-Hay: Abbvie: Consultancy;Servier: Other: Advisory Board, Speakers Bureau;Jazz: Other: Advisory Board, Speakers Bureau;Takeda: Speakers Bureau;Amgen: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Abatacept - off label use as GvHD prevention Cyclophosphamide - off label use as GvHD prevention
RESUMEN
Introduction: A hgher proportion of African American US veterans, compared to other racial-ethnic groups, with a high number of comorbidities was admtted to the John D. Dingell as there were no available sleep studies in this group. Results: Data on 50 patients are submtted here. Among 50 consecutive patents hospitalized with confirmed COVID-19 differences 0 had a diag c osis of OSA. significant predictor of hospital LOS was BMI (p=0.04), after adjusting for age, African-American (AA) race, chronic heart disease and the presence of OSA (model R-squared=0.15). saturation or time spent with SaO2<90% and the outcomes. Conclusion: Elevated BMI seemed to predict longer hospitalizations among COVID-19 veterans. Additional data collection is needed to assess the predictors of negative clinical outcomes in veterans with COVID-19 and OSA.
RESUMEN
Importance and Objective: The Covid pandemic is a timely opportunity to try to broaden our understanding of the links between education and health literacy and explore the vaccine-decision process with a view to identifying interventions that will positively influence vaccine uptake. EVIDENCE: Health and vaccine literacy encompass people's knowledge, motivation, and competence to access, understand, appraise and apply health information in order to make judgements and take decisions in everyday life concerning health care, disease prevention and health promotion. FINDINGS: Appropriate vaccine communication, which depends greatly on personal and contextual determinants, as well as on societal and environmental circumstances, is essential to reassure people about vaccine efficacy, safety, and possible side effects. However, vaccine confidence is not solely a question of trust in the vaccine's efficacy, safety. and individual protective benefit of vaccination. It also encompasses the mechanism(s) of vaccine activity, immunization schedules, organization and trust in the healthcare system that promotes and delivers the vaccines, and at what costs. When healthcare professionals as science brokers of vaccine knowledge attempt to increase vaccine knowledge and confidence, they must adjust their communication to the educational or health literacy level of their intended audience. Even if their messages are apparently clear and simple, they absolutely need to verify that they are properly understood. RELEVANCE: Specific vaccine communication training appears essential to increase vaccine communication skills among healthcare providers. Moreover, further randomized controlled studies are warranted to improve vaccine empowerment among different populations, from a variety of educational backgrounds.
Asunto(s)
Alfabetización en Salud , Envejecimiento Saludable , Vacunas , COVID-19 , Humanos , SARS-CoV-2RESUMEN
SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The pathophysiology of respiratory distress in hospitalized patients with COVID-19 is not yet fully understood. Spontaneous pulmonary barotrauma (PBT) is a pulmonary complication typically seen in intubated patients. However, in the related viral epidemic of SARS in 2002, 6.6% to 15% of patients on non-invasive ventilation (NIV) were described to have developed PBT, with severe alveolar destruction as the suggested mechanism. Within the COVID-19 pandemic, isolated case studies have described bulla and PBT, and a systematic review of imaging has suggested PBT to be a sign of disease progression. METHODS: In this single center retrospective case series, two patients with confirmed COVID-19 infection who developed PBT on NIV were identified in a New York City hospital from March 2020 to April 2020 and were included in this study. RESULTS: Both the patients were non-smokers with no pre-existing lung disease. The first patient was a 58-year-old woman with a history of pemphigus vulgaris, and the second patient was a 69-year-old man with a history of hypertension and type 2 diabetes mellitus. Both patients received treatment with hydroxychloroquine, azithromycin, therapeutic anticoagulation, high dose steroids, and were enrolled in the hospital’s remdesivir trial. Both patients required oxygen therapy which included escalation from nasal cannula to continuous positive airway pressure (CPAP), and both were encouraged to self-prone. The first patient was found to have a large left pneumothorax (PTX), pneumomediastinum (PM), and extensive subcutaneous emphysema (SE) on day 18 of hospitalization while on CPAP of 12 cm H2O, requiring surgical chest tube placement. The second patient developed a small left apical PTX, PM, and SE on day eight of hospitalization while on CPAP of 14 cm H2O, which was conservatively managed. Both patients eventually required intubation for worsening hypoxemia and later succumbed to their illness. CONCLUSIONS: In this study we identified two patients who developed PBT without being subjected to invasive ventilation or very high levels of PEEP. Both patients had poor outcomes, suggesting that COVID-19 may be associated with alveolar destruction, especially in the setting of steroid use. Glucocorticoid use may interfere with lung healing which could further increase the risk of alveolar rupture. CLINICAL IMPLICATIONS: This study encourages clinicians to have low threshold to suspect PBT in COVID-19 patients even while on NIV. Prospective studies are needed further to determine the utility of steroid use, given this potential risk for PBT and the clinical significance of our observations in COVID-19 patients. DISCLOSURES: No relevant relationships by Kirtipal Bhatia, source=Web Response No relevant relationships by Joseph Ghassibi, source=Web Response No relevant relationships by Julia Goldberg, source=Web Response No relevant relationships by Yasmin Herrera, source=Web Response No relevant relationships by Kam Sing Ho, source=Web Response No relevant relationships by Vivek Modi, source=Web Response No relevant relationships by Archana Pattupara, source=Web Response